2 Kidneys 10-12 cm retroperitoneal – behind the peritoneumnot part of the abdominal cavitysurrounded by three layers of tissue1. deepest layer = renal capsule – transparent sheet of dense irregular connective tissuecontinuous with the outer coat of the ureter2. middle layer = adipose capsuleamass of fatty tissue surrounding the renal capsule3. outer layer = renal fasciathin layer of dense irregular connective tissue that anchors the kidney to the abdominal walldivided internally into an outer cortex and an inner medullamedulla consists of 8 to 18 cone-shaped regions called renal pyramidsthe wider base faces towards the cortex, the narrow region (renal papilla) projects down into a cup-like structure called a minor calyxrenal cortex is divided into an outer cortical zone and a deeper juxtamedullary zonethe cortex also extends down in between the pyramids to form the renal columnsrenal lobe = renal pyramid + the overlying renal cortex + ½ the adjacent renal colum

3 Blood supply supplied by a renal artery and drained by a renal vein(s)kidney receives 20-25% of the resting cardiac output through the renal arteries (1200mL per minute)renal artery divides into segmental arteries – supply segments of the kidneythe segmental arteries give off branches that pass through the renal columns – interlobar arteriesat the base on the renal pyramids – between the medulla and cortex – they are called arcuate arteriesdivisions from the arcuate are called the interlobular arteries (pass between the renal lobes)the afferent arterioles are derived from the interlobular arteriesafferent arteriole supplies one nephron and forms the glomerulus (capillary network)drainage of the glomerulus is via the efferent arterioleefferent arteriole forms the peritubular capillary network which surround the upper portions of the nephronan extension of this network covers the lower portion of the nephron (loop of henle) – vasa rectathe peritubular capillaires form the interlobular veins – arcuate veins – interlobar veins – renal vein

5 Cortical Nephron 80-85% of nephrons are cortical nephronsRenal corpuscles are in outer cortex and loops of Henle lie mainly in cortex

6 Juxtamedullary Nephron15-20% of nephrons are juxtamedullary nephronsRenal corpuscles close to medulla and long loops of Henle extend into deepest medulla enabling excretion of dilute or concentrated urine

7 Urinary System Function1. Excretion of Metabolic Wastes: nitrogenous wastes-Urea: by-product of amino acid metabolism-produced when ammonia + carbon dioxide-Creatinine: produced by breakdown of creatine phosphate(high energy molecule reserve of muscles)-Uric acid: by-product of nucleotide breakdown-insoluble and ppts in the blood, concentrates in joints2. Water-Salt balance of blood: reabsorption into blood from the descendingLoop of Henle, from collecting duct-reclaim salt from the ascending portion of Loop of Henle-reclaim urea from bottom section of collecting duct-release of anti-diuretic hormone by pituitary: increase reabsorption of water3. Acid-Base balance of blood: reabsorption of bicarbonate ions from urine in thenephron decreases levels in blood (decreases carbonic acid levels)-movement of hydrogen ions from blood into the nephron, combineswith ammonia to form ammonium (NH4+)

8 4. Secretion of hormones: release of renin by kidneys which leadsto release of aldosterone by adrenal glands (reabsorption ofsalts by kidneys)-release of erythropoietin by kidneys (stimulates RBC production)-activation of vitamin D produced by the skin

9 Water Balance-extracellular fluids: blood plasma, interstitial fluid, CSF, etc….-intracellular fluids: cytosol-unique distribution of ions in ECF and ICFe.g. -intracellular fluids: higher potassium, phosphate, magnesium- lower sodium, chloride and bicarb ions than in extracellular fluid-of the 40 liters of water in the average male - 37% is ECF and 63%is ICF-so the kidney’s ability to modulate the composition of blood plasmacan determine the composition of interstitial fluid and therefore ICF

10 Water Intake-average intake L(60% from drinking water, 30% from moist foods, 10% byproductof metabolism)-regulation of intake - thirst center within the hypothalamuse.g. as body loses water - osmoreceptors within the thirst centerdetect increase in osmotic pressure within the ECF(increase as little as 1%)-drinking distends the stomach which inhibits signalling from thethirst center

11 Water output-loses through urine, feces and sweat plus respiration and skin evaporation-2.5 L of water must be lost for water balance-60% lost in urine, 6% in feces, 6% in sweat, 28% evaporationfrom skin and lungs-primary means of controlling output is through urine production-dehydration: ECF becomes concentrated - increase osmotic pressure- pressure increase detected by osmoreceptors in hypothalamus-posterior pituitary gland releases anti-diuretic hormone (ADH)-ADH causes distal convoluted tubule and collecting duct toincrease water reabsorption-excess water intake: ECF less concentrated - decrease in O.P-osmoreceptors signal to the post. pituitary-P.P decreases ADH release-kidney/nephrons decrease water reabsorption

12 Renal physiology comprised of filtration at the capsule (1)reabsorption through the tubules (2)direct secretion by the cells lining these tubules (3)

13 glomerulus: capillary tangle derived from afferent arterioles (into) and lead into efferent arterioles (out)surrounded by a glomerular capsule (Bowman’s capsule) – single layer of epithelial cellsglomerular capsule: site of initial filtration and the first step in the formation of urineconsists of visceral and parietal layersvisceral layer consists of modified epithelial cells = podocytesthe podocytes wrap around the endothelial cells of the glomerular capillaries and forms the filtration membrane together with the endothelial cell wallslits are covered with a slit membrane that permits the passage of small molecules such as water, vitamins, amino acids, wastes and small plasma proteinsspace between the visceral and parietal layers = glomerular capsulebetween the union of the afferent and efferent arterioles are mesangial cells that help regulate the rate of glomerular filtration

14 1. Glomerular filtrationRenal Physiology1. Glomerular filtrationdepends on three main pressures1. glomerular blood pressure (GBP) – BP in the glomerular capillaries (55 mmHg)promotes filtration by forcing water and solutes through the filtration membrane2. caspsular hydrostatic pressure (CHP) – hydrostatic pressure exerted against the filtration membrane by fluid already in the bowman’s capsuleopposes filtration from the blood15 mm Hg3. blood collioid osmotic pressure (BCOP) – due to the presence of plasma proteins in the blood30 mmHgnet filtration pressure (NFP) = GBP – CHP – BCOP = 10 mm Hgloss of plasma proteins in the urine can cause edema (increased interstitial fluid)damage to the glomerular capillaries can increase their permeabilty – loss of the larger plasma proteinsthis increases the BCOP which draws larger amounts of water out of the blood and into the urinebut the BCOP decreases because we are losing these plasma proteins in the urinethe overall drop in BCOP causes water to leave the blood and enter the tissues systemically

15 Glomerular filtration rateglomerular filtration rate (GFR) – amount of filtrate formed per minute (125 mL/min)affected dramatically by NFPadjusted by regulating: 1) blood flow into and out of the glomerulus and 2) the glomerular capillary surface area available for reabsorptionthree mechanisms control GFR

16 GFR1. renal autoregulation – two mechanisms – myogenic mechanism and tubuloglomerular feedbackmyogenic mechanism – increased blood volume can increased GFRby the stretching of the afferent arterioles triggers the contraction of the smooth muscle lining these arteriolestubulogomerular mechanism – feedback provided to the glomerulus from the renal tubulesincrease in the fluid through the PCT, LH and DCT – less time to reabsorb materialscells in these tubules induce vasoconstriction in the afferent arteriolesif GFR drops below normal – these cells stimulate the release of NO from the juxtaglomerular cells – vasodilation which increases blood flow and GFR2. neural regulation – sympathetic ANS fibers release norepinephrine which causes vasoconstriction of the smooth muscle in the afferent arteriole3. hormonal regulationrelease of angiotensin II reduces GFR by inducing vasoconstrictionalso release of atrial natriureic peptide (ANP – from the cardiac cells) increases GFP by increasing the surface area of the glomerulus

17 PCT and Loop of Henleproximal convoluted tubule: first area of reabsorption into blood -> Loop of Henle -> distal convoluted tubule -> collecting duct -> union of ducts into uretercells of these tubules are also single epithelial layers – vary as either cuboidal (PCT and DCT, descending) or squamous (ascending LH)PCT and DCT surrounded by the peritubular network of capillaries for reabsorption back into the blood, LH is covered with the vasa rectaPCT is the site of water reabsorption (PASSIVE) - associated with the ACTIVE reabsorption of sodium and potassium ionsactive Na+ and K+ uptake by the blood from the PCT is by sodium pumps - sodium pumped from the PCT and chloride, bicarbonate and phosphate ions follow it - salt reabsorptionthe active transport of ions into the blood plasma increases osmotic pressure within the bloodtherefore water moves out of the PCT into the capillaries PASSIVELY!PCT reabsorbs about 70% of filtered Na+, ions and waterthe apical surface of the PCT epithelium forms microvilli which increases the surface area of this region

18 Loop of Henleactive transport of Na+ continues through the loop of Henle and DCTdescending loop of Henle is quite permeable to water but impermeable to solute movement – urine becomes hypertonic (increased ions within the urine, decreased water)ascending loop is the opposite – permeable to salt (salt pumped out of the urine backinto the blood plasma)the wall of the arterioles alongside the ascending portion of the LH contain modified smooth muscle cells = juxtaglomerular cellsregulate blood pressure within the kidneys

19 DCT and Collecting Ducttwo types of cells found in the DCT and CDprincipal cells – receptors for ADH and aldosteroneintercalated cells – play a role in the homeostasis of blood pHDCT and collecting duct are impermeable to water !!!!the DCT and CD become permeable upon action of hormones

20 Renal Physiology Tubular reabsorptiontubule cells reabsorb about 99% of the filtered water and many of the solutesprincipal materials reabsorbed – glucose, aminao acids, urea, Na+, K+, Ca+, Cl-, HCO3- and HPO4-return to the blood through reabsorption into the peritubular capillary network and vasa rectareabsorption = return to the bloodabsorption = entrance of new materials into the blood (e.g. via digestive absorption)reabsorption routes – one of two routes before re-entering the blood

21 Reabsorption Routes Paracellular reabsorptionbetween adjacent tubule cells into the blood50% of reabsorbed material moves between cells by diffusion in some parts of tubuleTranscellular reabsorptionmaterial moves through both the apical and basal membranes of the tubule cell by active transport

22 Renal Physiology Tubular secretiontubular cells also secrete other materials – wastes, drugs, excess ions into the urinethis also removes these materials from the blood

23 Reabsorption in the PCTNa+ symporters help reabsorb materials from the tubular filtrateGlucose, amino acids, lactic acid, water-soluble vitamins and other nutrients are completely reabsorbed in the first half of the proximal convoluted tubuleIntracellular sodium levels are kept low due to Na+/K+ pumpReabsorption of Nutrients

25 Passive Reabsorption in the 2nd Half of PCTElectrochemical gradients produced by symporters & antiporters causes passive reabsorption of other solutesCl-, K+, Ca+2, Mg+2 and urea passively diffuse into the peritubular capillariesPromotes osmosis in PCT (especially permeable due to aquaporin-1 channels

26 Secretion of NH3 & NH4+ in PCTAmmonia (NH3) is a poisonous waste product of protein deamination in the livermost is converted to urea which is less toxicBoth ammonia & urea are filtered at the glomerus & secreted in the PCTPCT cells deaminate glutamine in a process that generates both NH3 and new bicarbonate ion.Bicarbonate diffuses into the bloodstreamduring acidosis more bicarbonate is generated

27 Reabsorption in the Loop of HenleTubular fluidPCT has reabsorbed 65% of the filtered water so chemical composition of tubular fluid in the loop of Henle is quite different from plasmasince many nutrients were reabsorbed as well, osmolarity of tubular fluid is close to that of blood

29 Symporters in the Loop of HenleThick limb of loop of Henle has Na+ K- Cl- symporters that reabsorb these ionsK+ leaks through K+ channels back into the tubular fluid leaving the interstitial fluid and blood with a negative chargeCations passively move to the vasa recta

30 Reabsorption in the DCTRemoval of Na+ and Cl- continues in the DCT by means of Na+ Cl- symportersNa+ and Cl- then reabsorbed into peritubular capillariesDCT is major site where parathyroid hormone stimulates reabsorption of Ca+2DCT is not very permeable to water so it is not reabsorbed with little accompanying water

31 Reabsorption & Secretion in the Collecting DuctBy end of DCT, 95% of solutes & water have been reabsorbed and returned to the bloodstreamCells in the collecting duct make the final adjustmentsprincipal cells reabsorb Na+ and secrete K+intercalated cells reabsorb K+ & bicarbonate ions and secrete H+

32 Actions of the Principal CellsNa+ enters principal cells through leakage channelsNa+ pumps keep the concentration of Na+ in the cytosol lowCells secrete variable amounts of K+, to adjust for dietary changes in K+ intakedown concentration gradient due to Na+/K+ pumpAldosterone increases this Na+ reabsorption (and passive water reabsorption) & K+ secretion by principal cells by stimulating the synthesis of new pumps and channels.

33 Secretion of H+ and Absorption of Bicarbonate by Intercalated CellsProton pumps (H+ATPases) secrete H+ into tubular fluidcan secrete against a concentration gradient so urine can be 1000 times more acidic than bloodCl-/HCO3- antiporters move bicarbonate ions into the bloodintercalated cells help regulate pH of body fluidsUrine is buffered by HPO4 2- and ammonia (secreted by cells of PCT), both of which combine irreversibly with H+ and are excreted

34 Production of Dilute or Concentrated UrineHomeostasis of body fluids despite variable fluid intakeKidneys regulate water loss in urineADH controls whether dilute or concentrated urine is formedif lacking, urine contains high ratio of water to solutesdilute urine – reabsorption of ions is unchanged (normal) but ADH decreases reabsorption of water

36 Renin-Angiotensin-Aldosteronewhen blood volume and BP drop – the walls of the afferent arterioles are stretched less – juxtaglomerular cells secrete renin into the blood (also stimulated by sympathetic stimulation)in the blood renin cleaves angiotensinogen (made by hepatocytes) to form angiotensin Ithe enzyme ACE (in the lung) – cleaves this even more to form angiotensin II1. decreases GFR by causing vasoconstriction of afferent arterioles2. enhances reabsorption of Na+, Cl+ and water in the PCT by stimulating the Na/H antiporter3. stimulates the release of aldosterone by the adrenal cortex – stimulates the principal cells of the DCT collecting ducts to reabsorb more Na and Cl and secrete more K into the bloodosmotic consequence of this causes an increased reabsorption of water

37 ADH and ANP ADH – released by the posterior pituitaryregulated water reabsorption by increasing the permeability of the principal cells in the DCT to waterin the absence of ADH the principal cells of the DCT and CT have low permeability to waterwithin the principal cells are vesicles containing a protein called aquaporin-2ADH stimulates the insertion of aquaporin-2 into the apical membranewater permeability increaseswhen the OP of the blood plasma increases (decreased water concentration ) via increased filtration – osmoreceptors in the hypothalamus detect this drop and stimulate the release of ADHincreased permability to water reintroduces water back into the blood and lower the OP of the blood plasmaANP – inhibits the reabsorption of Na and water in the PCT and the collecting ductalso suppresses the secretion of aldosterone and ADHincreases the excretion of Na in the urine (natriuresis) and increase urine output (diuresis) which decreases blood volume and BP and inhibits its further release